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The role of extracellular vesicle fusion with target cells in triggering systemic inflammation

Papareddy, Praveen LU orcid ; Tapken, Ines ; Kroh, Keshia ; Varma Bhongir, Ravi Kiran LU orcid ; Rahman, Milladur LU orcid ; Baumgarten, Maria LU ; Cim, Eda Irem ; Györffy, Lilla ; Smeds, Emanuel LU and Neumann, Ariane LU , et al. (2024) In Nature Communications 15.
Abstract

Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally... (More)

Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Mice, NF-kappa B/metabolism, Extracellular Vesicles/metabolism, Biological Transport, Signal Transduction, Inflammation/pathology
in
Nature Communications
volume
15
article number
1150
publisher
Nature Publishing Group
external identifiers
  • scopus:85184724486
  • pmid:38326335
  • pmid:38326335
ISSN
2041-1723
DOI
10.1038/s41467-024-45125-1
language
English
LU publication?
yes
id
aa4db098-f72d-47f1-a871-bd7aded86851
date added to LUP
2024-02-14 08:24:17
date last changed
2024-04-21 04:56:46
@article{aa4db098-f72d-47f1-a871-bd7aded86851,
  abstract     = {{<p>Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.</p>}},
  author       = {{Papareddy, Praveen and Tapken, Ines and Kroh, Keshia and Varma Bhongir, Ravi Kiran and Rahman, Milladur and Baumgarten, Maria and Cim, Eda Irem and Györffy, Lilla and Smeds, Emanuel and Neumann, Ariane and Veerla, Srinivas and Olinder, Jon and Thorlacus, Henrik and Ryden, Cecilia and Bartakova, Eva and Holub, Michal and Herwald, Heiko}},
  issn         = {{2041-1723}},
  keywords     = {{Animals; Mice; NF-kappa B/metabolism; Extracellular Vesicles/metabolism; Biological Transport; Signal Transduction; Inflammation/pathology}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{The role of extracellular vesicle fusion with target cells in triggering systemic inflammation}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-45125-1}},
  doi          = {{10.1038/s41467-024-45125-1}},
  volume       = {{15}},
  year         = {{2024}},
}